title: B cells as a therapeutic target for IFN-β in relapsing-remitting multiple sclerosis.
abstract: IFN-β-1b is a first-line immunomodulatory therapy for relapsing-remitting multiple sclerosis (RR MS). However, its effects on B cells have not been characterized. In vitro studies of B cells derived from RR MS patients revealed that IFN-β-1b decreases B cells' stimulatory capacity, as detected by inhibition of the Ag-specific T cell proliferative response upon Ag presentation by IFN-β-1b-treated B cells. Our study has identified that IFN-β-1b inhibited B cells' stimulatory capacity in RR MS patients and healthy controls through the suppression of CD40 and CD80 expression, whereas the MHC class I and II expression was not changed. IFN-β-1b in vitro treatment inhibited B cell secretion of IL-1β and IL-23 and induced IL-12 and IL-27. Supernatants transferred from IFN-β-1b-treated B cells inhibited Th17 cell differentiation, as they suppressed gene expression of the retinoic acid-related orphan nuclear hormone receptor C and IL-17A and secretion of IL-17A. In addition, IFN-β-1b induced B cells' IL-10 secretion, which may mediate their regulatory effect. Studies of B cells derived from RR MS patients treated with recombinant s.c. injected IFN-β-1b revealed that they induced a significantly lower proliferative response in allogenic MLR than the B cells from untreated patients. Further confirming the IFN-β-1b in vitro-induced changes in B cell cytokine secretion, B cells derived from the IFN-β-1b-treated patients secreted significantly lower levels of IL-1β and IL-23 and higher levels of IL-12 and IL-27 in comparison with the B cells derived from untreated patients. We conclude that IFN-β-1b exerts its therapeutic effects in part by targeting B cells' functions that contribute to the autoimmune pathogenesis of RR MS.
authors.affiliation: Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Vinod S
authors.initials: VS
authors.lastname: Ramgolam
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Sha
authors.forename: Karen L
authors.initials: KL
authors.lastname: Marcus
authors.forename: Neelima
authors.initials: N
authors.lastname: Choudhary
authors.forename: Luigi
authors.initials: L
authors.lastname: Troiani
authors.forename: Manisha
authors.initials: M
authors.lastname: Chopra
authors.forename: Silva
authors.initials: S
authors.lastname: Markovic-Plese
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000502:physiology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053759:Interleukin-23 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D053583:Interleukin-1beta; D053759:Interleukin-23; D016899:Interferon-beta; D000068556:Interferon beta-1a